The effect of increasing topotecan infusion from 30 minutes to 4 hours on the duration of exposure in cerebrospinal fluid

Zamboni, William C.; Lüftner, Diana; Egorin, Merrill J.; Schweigert, M.; Sezer, O.; Richter, Trevor; Natale, James; Possinger, K.

doi:10.1023/a:1008369615016

Cited by 19 publications

(13 citation statements)

References 7 publications

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“…The finding that topotecan given as a single drug has some activity in brain metastases of small cell lung cancer [15] and breast cancer [25], and the observation that it penetrates the blood-brain barrier [2,35] and sensitizes tumor cells against radiation [12,17] has stimulated several phase I/II trials which evaluated the use of combined radiochemotherapy with topotecan for brain metastases. Grueschow et al [7] treated 20 patients with a continuous i.v.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the limited tolerance of the normal brain tissue to radiation and a shallow radiation dose-response curve [24], increased doses of radiation have failed to improve outcome. Therefore, we evaluated the use of topotecan, a topoisomerase I inhibitor, which has been shown to penetrate the intact blood-brain barrier [2,35] and to sensitize tumor cells against radiation [12,17,33]. Toxicity and effectiveness were examined in a dose-escalating phase II trial where topotecan was infused daily before the radiation fractions in order to allow for a maximum of interaction between the damage-repair processes induced by radiation and the topoisomerase I inhibition.…”

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confidence: 99%

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Phase I/II Trial of Simultaneous Whole-Brain Irradiation and Dose-Escalating Topotecan for Brain Metastases

Köcher

Eich²,

Semrau³

et al. 2005

Strahlenther Onkol

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Phase I/II Trial of Simultaneous Whole-Brain Irradiation and Dose-Escalating Topotecan for Brain Metastases

Köcher

Eich²,

Semrau³

et al. 2005

Strahlenther Onkol

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“…Although, from the data presently available, topotecan is quite effective in AML, induction of continuous remission in AML by a single agent would be unlikely. [11][12][13][14] With respect to the second conditioning, since CNS radiation with 18 Gy alone had not been sufficient in the primary therapy, TBI with 12 Gy was probably not the key factor in prolonging remission after the second BMT.…”

Section: Discussionmentioning

confidence: 99%

Long-term remission of APL with a second allogeneic BMT after CNS relapse following HLA-identical allogeneic BMT

Classen

Debatin

Friedrich

et al. 2003

Bone Marrow Transplant

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Summary:Second allogeneic bone marrow transplantation (BMT) for AML relapsing after an initial BMT has a poor prognosis, with a probability of a 2-y disease-free survival below 30 per cent, caused both by treatment-related mortality (TRM) and high relapse rate. While TRM is most likely due to heavy pretreatment, AML relapse after BMT may be due to resistant disease or to a poor graftversus-leukaemia (GvL) effect of the transplant. The degree of GvL may depend on individual donor/recipient immunoreactivity. In most published cases of second allogeneic BMT, both transplants were performed from the same donor. Here, we describe a patient who was first transplanted for acute promyelocytic leukaemia (APL) (AML FAB M3v) from his HLA-identical brother and received intensive immunotherapy including donor lymphocytes and IL2. He remained free from GvHD 4I1, but developed CNS relapse. After a second BMT from another HLA-identical brother, he spontaneously developed GvHD III1, and has now been disease free for nearly 3 years. In this patient, long-term remission of AML relapsing after BMT was achieved by combining remission induction using an individual chemotherapy protocol with a second BMT from an alternative matched related donor and transient GvHD III1, which probably conferred a GVL effect. Bone Marrow Transplantation (2003) 32, 843-846. doi:10.1038/sj.bmt.1704225 Keywords: AML; APL; CNS-relapse; GvL Published data on second allogeneic transplants after leukaemia relapse indicate high treatment related mortalities (TRM) and relapse rates. [1][2][3][4] . In the most recently published series, a 2-year disease-free survival of 21% was found. 1 Munoz et al 3 reported five of 21 pediatric patients event-free at 5 years, with eight of 21 relapsing, and another eight of 21 dying from TRM. All except two had the same donor in both transplants. Bosi et al found an event-free survival of 26% at 5 years, with a TRM of 46%. 2 Late relapse, full conditioning, and remission before BMT were identified as good prognostic factors. 2 Other studies found even higher incidences of fatal complications. 4 The high rate of TRM can be attributed to heavy pretreatment in most patients. For leukaemia relapse, the main reasons may be resistant disease and an insufficient graft-versus-leukaemia (GvL) effect. Since the degree of GvL depends on the individual donor/recipient immunoreactivity, it is of interest to study cases of sequential bone marrow transplantations (BMTs) using different donors.Acute promyelocytic leukaemia (APL) or acute myelogeneous leukaemia, FAB M3, is caused by the chromosomal translocation t(15;17) leading to a fusion protein consisting of the growth suppressor protein PML and the retinoic acid receptor-a(RARa). 5,6 By inhibition of terminal differentiation in promyelocytes this protein leads to unlimited blast proliferation. The subtype FAB M3v, characterized by the microgranular morphology of the blasts, is associated with a high incidence of hyperleukocytosis and severe coagulopathy at presentation, and the prognosis ...

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“…Topotecan, a topoisomerase I inhibitor, crosses the BBB [63], as measurable levels of topotecan and its metabolite being detected in the cerebrospinal fluid (CSF). However, as topotecan is a multi-drug resistance pump substrate, and is found in high concentrations in rat glioma, the concentration decreases sharply as the distance from the tumor increases [33].…”

Section: Topotecanmentioning

confidence: 99%

Chemotherapy in breast cancer patients with brain metastases: Have new chemotherapic agents changed the clinical outcome?

Tosoni

Franceschi

Brandes

2008

Critical Reviews in Oncology/Hematology

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The effect of increasing topotecan infusion from 30 minutes to 4 hours on the duration of exposure in cerebrospinal fluid

Abstract: Prolonging TPT infusion from 30 minute to 4 hours increases the duration of exposure in the CSF. This study demonstrates the ability to develop treatment strategies of systemically administered chemotherapy to enhance cytotoxic exposure in the CSF.

Cited by 19 publications

References 7 publications

Phase I/II Trial of Simultaneous Whole-Brain Irradiation and Dose-Escalating Topotecan for Brain Metastases

Phase I/II Trial of Simultaneous Whole-Brain Irradiation and Dose-Escalating Topotecan for Brain Metastases

Long-term remission of APL with a second allogeneic BMT after CNS relapse following HLA-identical allogeneic BMT

Chemotherapy in breast cancer patients with brain metastases: Have new chemotherapic agents changed the clinical outcome?

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